Breadcrumb

Zampieri Lab

Development and Function of Neural Circuits

Profile

Our group is interested in understanding the logic and molecular mechanisms that control assembly and function of neural circuits. We approach this general problem by using as a model the sensory-motor system in the mouse spinal cord, which comprise relatively well-studied circuits that are genetically and anatomically accessible. We focus on two complementary lines of research to reveal how spinal circuits are first organized during development and then function in controlling locomotion and processing of somato-sensory information. In order to tackle these questions we combine mouse genetics, viral and anatomical tracing techniques with functional and behavioral experiments according to the following lines of research:

- Motor neuron organization and the assembly of circuit for locomotion.
- The functional organization of spinal somatosensory circuits.

Research

Motor neuron organization and the assembly of circuit for locomotion

The precise spatial organization of neurons in the nervous system is thought to be an important determinant of identity, connectivity and ultimately function. In the central nervous system (CNS), neurons are broadly arranged following two anatomical plans that involve laminar and nuclear organization, where distinct neuronal subtypes are often found in stereotyped positions that are predictive of their input-output connectivity patterns. A striking example of nuclear organization is apparent in the positioning of limb innervating motor neurons, which are grouped into discrete structures, termed motor pools, occupying conserved and stereotyped positions in the ventral spinal cord. Motor neurons grouped together not only share positional coordinates but also send projections to the same muscle targets in the periphery. Thus, precise spatial organization appears to represent a major strategy to simplify the problem of wiring the motor system. However, the molecular mechanisms controlling motor pool organization and its contribution to the assembly of spinal circuits are not fully understood. We address these problems using mouse genetics to generate models with scrambled motor neuron organization to study the mechanisms controlling precise positioning and then investigate the effects on circuit assembly and motor behavior.

The functional organization of spinal somato-sensory circuits

The ability to monitor changes in the environment and generate appropriate behavioral responses is critical for survival. A fundamental question in neuroscience regards the circuit logic that is used to detect a virtually unlimited amount of stimuli and encode them to create a coherent perception of the world. In particular, the somatosensory system is given the complicated task of encoding a wide variety of different information including pain, touch, itch, proprioception, interoception, and temperature sensation. Much progress has been made in the anatomical, physiological and genetic characterization of primary somatosensory neurons, leading to a quite extensive description of sensory neurons specialized in the detection of different stimuli. In comparison, little is know about how sensory modalities are encoded by spinal circuits to influence, locally, motor function and, in higher centers, our perception of somatic sensation. In particular, despite recent efforts in untangling the identity and function of interneurons participating to spinal somatosensory networks, circuit organization of sensory afferents encoding different modalities and their spinal targets are not clear. We seek to define, at anatomical and functional level, how distinct primary somatosensory neurons subtypes wire in the central nervous system to control processing of somatic information. In order to achieve this goal we combine mouse genetic, anatomical tracing and behavioral approaches to study spinal circuits controlling perception of somatic sensation and the generation of appropriate motor responses.